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Pharmaceutical composition intended for the treatment of a disease in which heterocyclic inhibitors of glycogen synthase kinase GSK-3 are involvedCM Patents

In the present invention, there is disclosed the use of thiadiazolidine derivative of the general formula II, in which: Rea and Reb are selected independently on each another from the group consisting of hydrogen, alkyl, cycloalkyl, haloalkyl, aryl being optionally substituted with a group being selected from the group consisting of alkyl, halogen and alkoxy, (Z)in-aryl, wherein the aryl moiety can be optionally substituted; Z is independently selected from the group consisting of -C(Re3)(Re4)-, -C(O)-, -O-, -C(=NRe3)-, -S(O)it- and N(Re3)-; n is zero, one or two; t is zero, one or two; Re3 and Re4 are selected independently on each another from the group consisting of hydrogen, alkyl, aryl and a heterocyclic radical; X and Y are selected independently on each another from the group consisting of =O, =S, =N(Re3) and =C(Re1)(Re2); and Re1 and Re2 are selected independently on each another from the group consisting of hydrogen, alkyl, cycloalkyl, haloalkyl, aryl, -(Z)in-aryl, an aromatic heterocyclic radical, -ORe3, -C(O)Re3, -C(O)ORe3, -(Z)in- C(O)ORe3 and -S(O)it-; for the preparation of a pharmaceutical composition intended for the treatment of a disease in which the heterocyclic inhibitors of glycogen synthase kinase GSK-3 are involved, including Alzheimer's disease or non-insulin dependent diabetes mellitus or a hyperproliferative disease such as cancer, tissue dysplasia or metaplasia, psoriasis, arteriosclerosis or restenosis.

Datos clave

CategoríaInvención

Índice de la ficha

Updated at
05/11/2026
Numero publicacion
EP.1286964.A1
Fecha publicacion
05/03/2003
Anio publicacion
2003

En detalle

Reivindicaciones

1. The use of a compound having the general formula (II): <img class="EMIRef" id="459537437-ib0021" /> wherein: R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, haloalkyl, aryl, -(Z)<n> -aryl, heteroaryl, -OR<3> , -C(O)R<3> , -C(O)OR<3> , and -(Z)<n> -C(O)OR<3> ; Z is independently selected from -C(R<3> )(R<4> )-, -C(O)-, -O-, -C(=NR<3> )-, -S(O)<t> - and -N(R<3> )-; n is zero, one or two; t is zero, one or two; R<3> and R<4> are independently selected from hydrogen, alkyl, aryl and heterocyclic; X and Y are independently selected from =O, =S, =N(R<3> ) and =C(R<1> )(R<2> ); and R<1> and R<2> are independently selected from hydrogen, alkyl, cycloalkyl, haloalkyl, aryl,-(Z)<n> -aryl, heteroaryl, -OR<3> , -C(O)R<3> , -C(O)OR<3> , and -(Z)<n> -C(O)OR<3> ; in the preparation of a pharmaceutical composition for a method of the treatment of a disease in which GSK-3 is involved, the method comprising administering to a human in need of such a treatment an effective amount of a compound of formula (II). 2. A use according to claim 1, where the disease is selected from Alzheimer's disease and non-insulin dependent diabetes mellitus. 3. A use according to claim 1, where the disease is a hyperproliferative disease such as cancer, displasias or metaplasias of tissue, psoriasis, arteriosclerosis or restenosis. 4. A use according to any preceding claim, wherein in the compound of formula (II), R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -C(R<3> )(R<4> )-aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), -OR<3> , -C(O)OR<3> and -C(R<3> )(R<4> )-C(O)OR<3> , and R<3> and R<4> are independently selected from hydrogen, alkyl and heterocyclic. 5. A use according to claim 4, wherein in the compound of formula (II), R<a> and R<b> are independently selected from alkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -CH<2> -aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), and -CH<2> C(O)OR<3> , and R<3> is hydrogen or alkyl. 6. A use according to claim 5, wherein in the compound of formula (II), R<a> and R<b> are independently selected from methyl, ethyl, propyl, benzyl, phenyl (optionally substituted with a group selected from methyl, fluoro, chloro, bromo and methoxy) and -CH<2> C(O)O-ethyl. 7. A use according to claim 1, 2 or 3, wherein in the compound of formula (II), X and Y are independently selected from =O, =S and =NR<3> (wherein R<3> is heterocyclic). 8. A use according to claim 7, wherein in the compound of formula (II), X is =O. 9. A use according to claim 8, wherein in the compound of formula (II), X is =O and Y is =O. 10. A use according to any one of claims 1, 2 or 3, wherein: R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -C(R<3> )(R<4> )-aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), -OR<3> , -C(O)OR<3> and -C(R<3> )(R<4> )-C(O)OR<3> , R<3> and R<4> are independently selected from hydrogen, alkyl and heterocyclic, and X and Y are independently selected from =O, =S and =NR<3> . 11. A use according to claim 10, wherein: R<a> and R<b> are independently selected from hydrogen, alkyl, cycloalkyl, aryl (optionally substituted with a group selected from alkyl, halo and alkoxy), -C(R<3> )(R<4> )-aryl (the aryl part being optionally substituted with a group selected from alkyl, halo and alkoxy), -OR<3> ,-C(O)OR<3> and -C(R<3> )(R<4> )-C(O)OR<3> , R<3> and R<4> are independently selected from hydrogen and alkyl; and X is = O. 12. A use according to claim 11, wherein: R<a> and R<b> are independently selected from methyl, ethyl, propyl, benzyl, phenyl (optionally substituted with a group selected from methyl, fluoro, chloro, bromo and methoxy) and-CH<2> -C(O)O-ethyl; X is =O; and Y is =O. 13. A use according to any of claims 1 to 3, wherein the compound of Formula (II) fits one of the following possibilities: CH<2>Ph Me O O Et Me O O Et nPr O O Et cyclohexyl O O Ph Me O O CH<2>CO<2>Et Me O O 4-OMePh Me O O CH<2>Ph Et O O Et iPr O O CH<2>Ph Et O S CH<2>Ph CH<2>Ph O S Ph Ph O S Et Et O S Cyclohexyl Me O O 4-MePh Me O O 4-BrPh Me O O 4-FPh Me O O 4-ClPh Me O O Et Me <img class="EMIRef" id="459537437-ib0022" /> O Et Et <img class="EMIRef" id="459537437-ib0023" /> O Et H <img class="EMIRef" id="459537437-ib0024" /> O Me Me <img class="EMIRef" id="459537437-ib0025" /> O Et Me <img class="EMIRef" id="459537437-ib0026" /> O Et Me <img class="EMIRef" id="459537437-ib0027" /> O Et Me <img class="EMIRef" id="459537437-ib0028" /> O Et Me <img class="EMIRef" id="459537437-ib0029" /> S 14. A use according to claim 13, wherein the compound of Formula (II) fits one of the following possibilities: CH<2>Ph Me O O Et Me O O Ph Me O O CH<2>CO<2>Et Me O O 4-OMePh Me O O 4-MePh Me O O 4-BrPh Me O O 4-FPh Me O O 4-CIPh Me O O CH<2>Ph CH<2>Ph O S Ph Ph O S 15. A pharmaceutical formulation containing as active ingredient a compound of formula (II) as defined in any of claims 1 to 14. 16. A compound having the general formula (II): <img class="EMIRef" id="459537437-ib0030" /> where the compound is one of the following: CH<2>Ph Me O O CH<2>CO<2>Et Me O O 4-OMePh Me O O 4-MePh Me O O 4BrPh Me O O

Etiquetas

Inventores
Martinez Gil AnaMartinez Gil, AnaCastro Morera, AnaCastro Morera AnaPerez Martin, Maria ConcepcionPerez Martin Maria ConcepcionCascon Mercedes AlonsoCascon, Mercedes AlonsoDiaz, IsabelDiaz IsabelMoreno Munoz Francisco JoseMoreno Munoz, Francisco JoseWandosell JuradoWandosell, JuradoMorera Ana CastroAna Castro MoreraMartin Maria Concepcion PerezMaria Concepcion Perez MartinMercedes Alonso CasconDiaz Isabel DorronsoroIsabel Dorronsoro DiazMunoz Francisco Jose MorenoFrancisco Jose Moreno MunozJurado Francisco WandosellWandosell Jurado FranciscoGil Ana MartinezAna Martinez GilFrancisco Wandosell JuradoMoreira Ana CastroAna Castro MoreiraDiaz, Isabel DorronsoroWandosell, Jurado FranciscoConcepcion Perez Martin MariaMARTINEZ, Gil, AnaCASTRO MORERA, AnaPEREZ MARTIN, Maria ConcepciónPerez Martin Maria ConcepciónCASCON, Mercedes AlonsoDIAZ, Isabel, DorronsoroMORENO MUNOZ, Francisco JoseWANDOSELL, JURADO, FranciscoPérez Martin Maria ConcepciónCascón Mercedes AlonsoDíaz Isabel DorronsoroMoreno Muňoz Francisco JosePurez Martin Maria ConcepcionPerez Martin, MariaPerez Martin MariaWandosell, Jurado, FranciscoDiaz, Isabel, DorronsoroAlonso Cascon MercedesAlonso Cascon, MercedesDorronsoro Diaz, IsabelDorronsoro Diaz IsabelPerez Martin, Maria ConcepciónWandosell Jurado, Francisco마르티네즈길아나카스트로모레라아나페레츠마틴마리아콘셉시온카스콘메르세데스알론소디아즈이자벨도론소로모레노뮤노즈프란시스코호세완도슬쥬라도프란시스코Moreno Munzo Francisco JoseМАРТИНЕС ХИЛЬ Ана(ES)Martines Khil AnaKastro Morera AnaКАСТРО МОРЕРА Ана(ES)Peres Martin Marija KonsepsionПЕРЕС МАРТИН Мари Консепсион(ES)КАСКОН Мерседес Алонсо(ES)Kaskon Mersedes AlonsoDias Isabel DorronsoroДИАС Исабель Дорронсоро(ES)МОРЕНО МУНЬОС Франсиско Хосе(ES)Moreno Mun Os Fransisko KhoseВАНДОСЕЛЛЬ ХУРАДО Франсиско(ES)Vandosell Khurado FransiskoPerez Maria Concepcion MartinMartinez AnaMartin Perez Maria ConcepcionMartinez Ana GilGil Ana MGil Ana M.Morera Ana CMorera Ana C.Perez Maria C MPerez Maria C.M.Cascon Mercedes ACascon Mercedes A.Diaz Isabel D.Diaz Isabel DMoreno Munoz Francisco J.Moreno Munoz Francisco JJurado Francisco WJurado Francisco W.
Solicitantes
Consejo Superior de Investigaciones CientíficasUniversidad Autónoma de MadridKonsekho Superior Investigasiones S'EntifikasKonsekho Superior InvestigasioRuffles, Graham, Keith
Clasificacion ipc
A61K 31/ 122 A IA61K 31/ 4015 A IA61K 31/ 4035 A IA61K 31/ 4196 A IA61K 31/ 426 A IA61K 31/ 433 A IA61K 31/ 4439 A IA61P 17/ 06 A IA61P 25/ 28 A IA61P 31/ 00 A IA61P 3/ 10 A IA61P 35/ 00 A IA61P 43/ 00 A IA61P 9/ 10 A IC07C 49/ 395 A IC07C 49/ 597 A IC07D 207/ 448 A IC07D 207/ 44 A IC07D 207/ 456 A IC07D 209/ 48 A IC07D 249/ 12 A IC07D 277/ 20 A IC07D 277/ 36 A IC07D 285/ 08 A IC07D 417/ 12 A IA61K 31/ 4427 A IA61P 25/ 00 A IA61P 3/ 00 A IC07D 285/ 13 A IA61K 31/ 44 A IA61K 31/ 4523 A IA61K 31/ 41 A IA61K 31/ 4436 A IA61K 31/ 4535 A IC07D 417/ 04 A I
Clasificacion cpc
514/351514/361514/362514/425514/445514/473548/128548/129548/135548/545549/62514/363514/364514/384514/326514/342546/209546/268.7548/130
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